TY - JOUR
T1 - Long-Duration Complete Remissions of Diffuse Large B Cell Lymphoma after Anti-CD19 Chimeric Antigen Receptor T Cell Therapy
AU - Kochenderfer, James N.
AU - Somerville, Robert P.T.
AU - Lu, Tangying
AU - Yang, James C.
AU - Sherry, Richard M.
AU - Feldman, Steven A.
AU - McIntyre, Lori
AU - Bot, Adrian
AU - Rossi, John
AU - Lam, Norris
AU - Rosenberg, Steven A.
N1 - Funding Information:
We thank the NIH Clinical Center 3 Northwest Nursing Unit nurses and our patients. We also thank Tyler Willett for help in organizing patient specimen shipments. This work was supported in part by intramural funding from the NIH National Cancer Institute Center for Cancer Research . The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. The work was also supported in part by Kite Pharma, Inc. through a cooperative research and development agreement with the NCI Surgery Branch .
Publisher Copyright:
© 2017
PY - 2017/10/4
Y1 - 2017/10/4
N2 - T cells expressing anti-CD19 chimeric antigen receptors (CARs) can induce complete remissions (CRs) of diffuse large B cell lymphoma (DLBCL). The long-term durability of these remissions is unknown. We administered anti-CD19 CAR T cells preceded by cyclophosphamide and fludarabine conditioning chemotherapy to patients with relapsed DLBCL. Five of the seven evaluable patients obtained CRs. Four of the five CRs had long-term durability with durations of remission of 56, 51, 44, and 38 months; to date, none of these four cases of lymphomas have relapsed. Importantly, CRs continued after recovery of non-malignant polyclonal B cells in three of four patients with long-term complete remissions. In these three patients, recovery of CD19+ polyclonal B cells took place 28, 38, and 28 months prior to the last follow-up, and each of these three patients remained in CR at the last follow-up. Non-malignant CD19+ B cell recovery with continuing CRs demonstrated that remissions of DLBCL can continue after the disappearance of functionally effective anti-CD19 CAR T cell populations. Patients had a low incidence of severe infections despite long periods of B cell depletion and hypogammaglobulinemia. Only one hospitalization for an infection occurred among the four patients with long-term CRs. Anti-CD19 CAR T cells caused long-term remissions of chemotherapy-refractory DLBCL without substantial chronic toxicities. Five of seven patients receiving anti-CD19 chimeric antigen receptor (CAR) T cells obtained complete remissions. Four of the five CRs had long-term durability with durations of remissions ranging from 38 to 56 months. Remissions persisted despite recovery of normal B cells in three of the four patients with long-term remissions.
AB - T cells expressing anti-CD19 chimeric antigen receptors (CARs) can induce complete remissions (CRs) of diffuse large B cell lymphoma (DLBCL). The long-term durability of these remissions is unknown. We administered anti-CD19 CAR T cells preceded by cyclophosphamide and fludarabine conditioning chemotherapy to patients with relapsed DLBCL. Five of the seven evaluable patients obtained CRs. Four of the five CRs had long-term durability with durations of remission of 56, 51, 44, and 38 months; to date, none of these four cases of lymphomas have relapsed. Importantly, CRs continued after recovery of non-malignant polyclonal B cells in three of four patients with long-term complete remissions. In these three patients, recovery of CD19+ polyclonal B cells took place 28, 38, and 28 months prior to the last follow-up, and each of these three patients remained in CR at the last follow-up. Non-malignant CD19+ B cell recovery with continuing CRs demonstrated that remissions of DLBCL can continue after the disappearance of functionally effective anti-CD19 CAR T cell populations. Patients had a low incidence of severe infections despite long periods of B cell depletion and hypogammaglobulinemia. Only one hospitalization for an infection occurred among the four patients with long-term CRs. Anti-CD19 CAR T cells caused long-term remissions of chemotherapy-refractory DLBCL without substantial chronic toxicities. Five of seven patients receiving anti-CD19 chimeric antigen receptor (CAR) T cells obtained complete remissions. Four of the five CRs had long-term durability with durations of remissions ranging from 38 to 56 months. Remissions persisted despite recovery of normal B cells in three of the four patients with long-term remissions.
KW - adoptive T cell therapy
KW - chimeric antigen receptors
KW - lymphoma
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U2 - 10.1016/j.ymthe.2017.07.004
DO - 10.1016/j.ymthe.2017.07.004
M3 - Article
C2 - 28803861
AN - SCOPUS:85028330613
SN - 1525-0016
VL - 25
SP - 2245
EP - 2253
JO - Molecular Therapy
JF - Molecular Therapy
IS - 10
ER -